X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function.

PURPOSE To assess the frequency of RPGR and RP2 mutations in a set of 85 patients with X-linked retinitis pigmentosa (XLRP) and to compare the visual function of patients with mutations in RPGR versus RP2. METHODS Eighty-five unrelated patients with XLRP were ascertained, mainly from North America. The single-strand conformation polymorphism (SSCP) and a direct sequencing technique were used to screen their DNA for mutations in the coding region and splice sites of RPGR and RP2. The Snellen visual acuities, visual field areas, and 0.5-Hz and 30-Hz electroretinograms (ERGs) were measured in male patients. The visual function parameters were compared using multiple regression analysis. RESULTS A wide spectrum of mutations was found in both genes, including missense, nonsense, splice-site, and frameshift mutations. Twenty putative pathogenic mutations in RPGR, 15 of which were novel, were found in 22 patients (26%), whereas 6 mutations in RP2, 4 of which were novel, were found in 6 patients (7%). A high fraction of the mutations in both genes affected amino acid residues within or adjacent to presumed functional domains. Comparison of visual function between comparably aged patients with mutations in RPGR versus RP2 showed that, on average, patients with RPGR mutations have lower ERG amplitudes and smaller visual field areas. CONCLUSIONS Mutations in RPGR and RP2 genes together account for approximately 33% of cases of XLRP in North America. Patients with RPGR mutations have less overall retinal function on average than those with RP2 mutations, on the basis of measurements of visual field areas and full-field ERG amplitudes.